AIDS, which has killed approximately 65,000 Americans over the past eight years is characterized by a severe imbalance of the immune system caused by the infection of helper/inducer T cells by the human immunodeficiency virus HIV. This retrovirus replicates through a DNA intermediate, and the synthesis of DNA complementary to viral DNA is catalyzed by a HIV-encoded polymerase, reverse transcriptase, a prime candidate for inhibition by AIDS-targeted drugs. 2',3'-Dideoxynucleosides like 3'-azido-2',3'- dideoxythimidine (AZT) are efficient substrate inhibitors of HIV reverse transcriptase, and their incorporation leads to DNA chain termination and inhibition of viral replication. For intracellular activation, the dideoxynucleosides must be phosphorylated by cellular nucleoside kinases to yield the active 5'-triphosphates. This application proposes the development of selective synthetic carriers for the transport of 5'-phosphorylated AIDS drugs across cell membranes. The new carriers incorporate recent advances in stereoelectronic effects and molecular shape. Specific recognition elements of the carriers include complementary hydrogen bonding edges and a hydrophobic site (an aromatic sheet or an apolar cyclophane cavity) for the purine or pyrimidine base, and cationic sites to bind to the phosphate functions. General synthetic protocols outlined are expected to allow the development of specific carriers for the delivery of a wide range of dideoxynucleoside-5'- triphosphates across membranes. The selectivity in recognition will be defined in NMR titrations, extraction experiments, and microcalorimetric measurements. The transport efficiencies of mononucleoside-5'-triphosphates and oligonucleotides through liquid organic membranes should provide a means by which the carrier properties of the new receptors could be refined. The described projects intend to provide a general solution to the efficient transport of these compounds across cell membranes. This may open new perspectives in AIDS therapy and widen the number of drug candidates to be considered for fighting this deadly disease.